Normal Development - Milk

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Introduction

Adult female mammary anatomy cartoon

Breast milk makes us mammals! This current page discusses some issues related to milk and neonatal nutrition, it is not a guide to breastfeeding, which is covered by many other resources. The composition of milk can vary over time, with colostrum the initial yellowish, sticky breast milk produced at the end of pregnancy.

The review article (abstract shown below) by Goldman in 2000[1] may provide a way of thinking about gastrointestinal tract and human milk.

There are other resource pages that cover the topic of breast development (More? mammary gland). Milk also has important role in gastrointestinal tract postnatal development (More? gastrointestinal tract)


Postnatal Links: birth | neonatal | neonatal diagnosis | milk | Nutrition | growth charts | Disease School Exclusion | vaccination | puberty | genital
| Nutrition

Some Recent Findings

  • The human milk microbiota[2] "Human milk has been traditionally considered sterile; however, recent studies have shown that it represents a continuous supply of commensal, mutualistic and/or potentially probiotic bacteria to the infant gut. Culture-dependent and -independent techniques have revealed the dominance of staphylococci, streptococci, lactic acid bacteria and bifidobacteria in this biological fluid, and their role on the colonization of the infant gut. These bacteria could protect the infant against infections and contribute to the maturation of the immune system, among other functions."
  • Breast milk hormones and regulation of glucose homeostasis[3] "Growing evidence suggests that a complex relationship exists between the central nervous system and peripheral organs involved in energy homeostasis. ...Several hormones, such as leptin, adiponectin, resistin, and ghrelin, are involved in this complex regulation. These hormones play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, and metabolic syndrome. Recently, their presence in breast milk has been detected, suggesting that they may be involved in the regulation of growth in early infancy and could influence the programming of energy balance later in life. This paper focuses on hormones present in breast milk and their role in glucose homeostasis."
  • Bioactive proteins in human milk: mechanisms of action[4] "Human milk contains a multitude of bioactive proteins, with very diverse functions. Some of these proteins are involved in the synthesis and expression of milk, but the majority appears to have evolved to provide physiological activities in the breast-fed infant. These activities are exerted by a wide variety of mechanisms and have largely been unraveled by in vitro studies. To be active in the gastrointestinal tract, these proteins must be able to resist proteolytic degradation, at least for some time. We have evaluated the human milk proteins lactoferrin, haptocorrin, alpha(1)-antitrypsin, and transforming growth factor -beta in an in vitro digestion model, mimicking the conditions of the infant gastrointestinal milieu. These bioactive proteins are resistant against proteolysis and can remain intact or as larger fragments through passage of the gastrointestinal tract. In vitro digestibility assays can be helpful to assess which human milk proteins can resist proteolysis and to what extent."

Mammary Glands Pregnancy

During pregnancy raised estrogens and progesterone stimulate gland development, secretory alveolar structures form and differentiate, leading to milk production in late pregnancy and milk secretion during lactation. Breasts are hemispherical in shape due to fat deposition. After birth, neonatal lactation supports further growth/development.


Links: Integumentary Development - Mammary Glands

Milk Composition

Hydrolysis of lactose

Most mammals produce milk containing similar components which may occur at different concentrations. Composition of the maternal diet can affect the concentration of some of these components. In addition, some materal environmental components can also appear in the milk.

Typical secreted milk contains:

  • Carbohydrate: lactose, glucose, galactose, and oligosaccharides
  • Electrolytes
  • Fats: triglycerides and fatty acids (omega-3 polyunsaturated fatty acids, such as docosahexanoic acid)
  • Minerals
  • Proteins: caseins, alpha-lactalbumin, immunoglobulins, albumin, lactoferrin, nonprotein nitrogen, enzymes, hormones, growth factors, and nucleotides
  • Trace elements: selenium and iodine
  • Vitamins: A, B1 (thiamin), B2 (riboflavin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), D, and E
  • Water

Lactoferrin

A bioactive protein in mammal milk with various neonatal actions, such as anti-infective, immunological, and gastrointestinal.[5]


Human Milk

"Human milk contains agents that affect the growth, development and functions of the epithelium, immune system or nervous system of the gastrointestinal tract. Some human and animal studies indicate that human milk affects the growth of intestinal villi, the development of intestinal disaccharidases, the permeability of the gastrointestinal tract and resistance to certain inflammatory/immune-mediated diseases. Moreover, one cytokine in human milk, interleukin (IL)-10, protects infant mice genetically deficient in IL-10 against an enterocolitis that resembles necrotizing enterocolitis (NEC) in human premature infants.

There are seven overlapping evolutionary strategies regarding the relationships between the functions of the mammary gland and the infant’s gastrointestinal tract as follows:

  1. certain immunologic agents in human milk compensate directly for developmental delays in those same agents in the recipient infant
  2. other agents in human milk do not compensate directly for developmental delays in the production of those same agents, but nevertheless protect the recipient
  3. agents in human milk enhance functions that are poorly expressed in the recipient
  4. agents in human milk change the physiologic state of the intestines from one adapted to intrauterine life to one suited to extrauterine life
  5. some agents in human milk prevent inflammation in the recipient’s gastrointestinal tract
  6. survival of human milk agents in the gastrointestinal tract is enhanced because of delayed production of pancreatic proteases and gastric acid by newborn infants, antiproteases and inhibitors of gastric acid production in human milk, inherent resistance of some human milk agents to proteolysis, and protective binding of other factors in human milk
  7. growth factors in human milk aid in establishing a commensal enteric microflora"

(Text from: Goldman AS. Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective.[1])

Immunity

In addition to maternal antibodies, milk contains maternal lymphocytes (antibody-producing B cells. T cells, and natural killer cells). In a mouse model, maternal cytotoxic T cells within milk have been shown to transfer into to the neonatal intestinal Peyer's patches.Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title

The neonatal immune system (innate and adaptive) is immature and still developing, and there is now good evidence that milk contributes to the developmental process, see review.[6]

Milk Production

Development of the breasts and milk production is mainly regulated by the anterior pituitary hormone prolactin (PRL). The release of prolactin is regulated by the hypothalamus prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP)

Prolactin hormone other roles include:

  • regulating follicle stimulating hormone (FSH) effect on the ovary.
  • increased maternal myelination processes during pregnancy.

Prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP) is an 87 amino acid peptide hypothalamus hormone which regulates anterior pituitary release of prolactin.

Prolactin signaling Pathway

In the mammary gland:

  1. Prolactin binds to its receptor (PRLR) and causes them to dimerize.
  2. Receptor-associated tyrosine kinase Jak2 phosphorylates: the prolactin receptor and Stat5a and Stat5b (signal transducers and activators of transcription).
  3. Activated Stat5a and -5b are transported into the nucleus
  4. They specifically bind DNA of target genes (the GAS sequence, TTCNNNGAA).
  5. Induce transcription that promote: proliferation, differentiation, and lactogenesis.

Environmental Contaminants

Environmental components (contaminants) that appear in the milk may depend on the origin (maternal, cow) or the water quality used in formula preparation.

Lead

  • Lead levels in human milk and children's health risk: a systematic review [7]
  • Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother[8] "The levels of lead in breast milk are thus similar to those in plasma. Breast-fed infants are only at risk if the mother is exposed to high concentrations of contaminants either from endogenous sources such as the skeleton or exogenous sources."
  • Effect of breast milk lead on infant blood lead levels at 1 month of age[9]


Links: Lead | Abnormal Development - Heavy Metals

Organic Pollutants

  • polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB)[10][11]

Abnormalities

Galactorrhoea

Galactorrhoea is the clinical term for inappropriate production of milk that is often associated with anterior pituitary tumours producing excess prolactin. This condition can occur in both females and males.

Galactosaemia

In galactosaemia babies cannot process galactose, a component of lactose. Incidence is about 1 in 40,000 births (about 1-3 cases per year). Life-threatening liver failure and infections can occur. A galactose-free diet instituted in the first postnatal week can be life saving.


Necrotizing Enterocolitis

Necrotizing Enterocolitis (NE) is the death of intestinal tissue that occurs postnatally in mainly in premature and low birth weight infants (1 in 2,000 - 4,000 births). The underdeveloped gastointestinal tract appears to be susceptible to bacteria, normally found within the tract, to spread widely to other regions where they damage the tract wall and may enter the bloodstream.

References

  1. 1.0 1.1 Goldman AS. (2000). Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective. J. Nutr. , 130, 426S-431S. PMID: 10721920
  2. Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R & Rodríguez JM. (2013). The human milk microbiota: origin and potential roles in health and disease. Pharmacol. Res. , 69, 1-10. PMID: 22974824 DOI.
  3. Savino F, Liguori SA, Sorrenti M, Fissore MF & Oggero R. (2011). Breast milk hormones and regulation of glucose homeostasis. Int J Pediatr , 2011, 803985. PMID: 21760816 DOI.
  4. Lönnerdal B. (2010). Bioactive proteins in human milk: mechanisms of action. J. Pediatr. , 156, S26-30. PMID: 20105661 DOI.
  5. Manzoni P, Dall'Agnola A, Tomé D, Kaufman DA, Tavella E, Pieretto M, Messina A, De Luca D, Bellaiche M, Mosca A, Piloquet H, Simeoni U, Picaud JC & Del Vecchio A. (2018). Role of Lactoferrin in Neonates and Infants: An Update. Am J Perinatol , 35, 561-565. PMID: 29694997 DOI.
  6. Cacho NT & Lawrence RM. (2017). Innate Immunity and Breast Milk. Front Immunol , 8, 584. PMID: 28611768 DOI.
  7. Koyashiki GA, Paoliello MM & Tchounwou PB. (2010). Lead levels in human milk and children's health risk: a systematic review. Rev Environ Health , 25, 243-53. PMID: 21038758
  8. Gulson BL, Jameson CW, Mahaffey KR, Mizon KJ, Patison N, Law AJ, Korsch MJ & Salter MA. (1998). Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother. Environ. Health Perspect. , 106, 667-74. PMID: 9755144
  9. Ettinger AS, Téllez-Rojo MM, Amarasiriwardena C, Bellinger D, Peterson K, Schwartz J, Hu H & Hernández-Avila M. (2004). Effect of breast milk lead on infant blood lead levels at 1 month of age. Environ. Health Perspect. , 112, 1381-5. PMID: 15471729
  10. Tanabe S & Kunisue T. (2007). Persistent organic pollutants in human breast milk from Asian countries. Environ. Pollut. , 146, 400-13. PMID: 16949712 DOI.
  11. LaKind JS, Berlin CM, Sjödin A, Turner W, Wang RY, Needham LL, Paul IM, Stokes JL, Naiman DQ & Patterson DG. (2009). Do human milk concentrations of persistent organic chemicals really decline during lactation? Chemical concentrations during lactation and milk/serum partitioning. Environ. Health Perspect. , 117, 1625-31. PMID: 20019916 DOI.


Journals

Reviews

Cacho NT & Lawrence RM. (2017). Innate Immunity and Breast Milk. Front Immunol , 8, 584. PMID: 28611768 DOI.

Garofalo R. (2010). Cytokines in human milk. J. Pediatr. , 156, S36-40. PMID: 20105664 DOI.

Lapillonne A & Jensen CL. (2009). Reevaluation of the DHA requirement for the premature infant. Prostaglandins Leukot. Essent. Fatty Acids , 81, 143-50. PMID: 19577914 DOI.

Bombell S & McGuire W. (2009). Early trophic feeding for very low birth weight infants. Cochrane Database Syst Rev , , CD000504. PMID: 19588318 DOI.

McClellan HL, Miller SJ & Hartmann PE. (2008). Evolution of lactation: nutrition v. protection with special reference to five mammalian species. Nutr Res Rev , 21, 97-116. PMID: 19087365 DOI.

Ogra PL. (2009). Developmental aspects of the mucosal immune system: role of external environment, mucosal microflora and milk. Adv. Exp. Med. Biol. , 639, 41-56. PMID: 19227533 DOI.

Wagner CL, Taylor SN & Johnson D. (2008). Host factors in amniotic fluid and breast milk that contribute to gut maturation. Clin Rev Allergy Immunol , 34, 191-204. PMID: 18330727 DOI.

Kent JC. (2007). How breastfeeding works. J Midwifery Womens Health , 52, 564-70. PMID: 17983993 DOI.

Van de Perre P. (2003). Transfer of antibody via mother's milk. Vaccine , 21, 3374-6. PMID: 12850343

Articles

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Search Pubmed: Mammary Gland Development | lactation | human milk | milk | breastfeeding

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Cite this page: Hill, M.A. (2018, November 15) Embryology Normal Development - Milk. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Normal_Development_-_Milk

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G